the risk of tuberculous infection in the netherlands from 1967 to 1979

Tubercle 64 (1983) 241-253 6 Longman Group Ltd.

THE RISK OF TUBERCULOUS INFECTION IN THE NETHERLANDS FROM 1967 TO 1979*

Ian Sutherland Medical Research Council Biostatistics Unit,

Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, England

M. A. Bleiker, J. Meijert and K. Stqblo KNCV (Royal Netherlands Tuberculosis Association), Postbus 146, Riouwstraat 7, The Hague, Netherlands

Summary Estimates of the annual risks of tuberculous infection in the Netherlands from 1910 to 1966 were made by Sf$blo et al. [l] from tuberculin surveys in recruits and schoolchildren. The risk decreased particularly steeply after about 1940 (the annual decrease in log risk was about 13 %),and forward projections of the risk were made on this basis to 1980.

Tuberculin test results in male recruits and in secondary or primary schoolchildren between 1966 and 1979 have now been used, alone and in conjunction with the earlier material, to estimate the trend in the risk of tuberculous infection in the Netherlands up to 1979, and to studythe sex and age patterns in the risk.

The risk of infection has continued to decrease steeply with calendar year in the Netherlands. Among the recruits the log risk, estimated only from the data from 1966 to 1979, decreased annually by 10.4%, compared with the estimate of 13.7 % from the earlier data from 1956 to1 966; this difference is non-significant.

Analysis of the complete data on schoolchildren from 1956 to 1979shows a decrease in their log risk of infection of 15.0% each calendar year. The risks of infection were similar for boys and girls up to age 10, but were higher for boys than for girls (by1 0.2 %) during adolescence. In addition there was an increase in log risk of about 6.1 % for each year of age up to age 20. According to this analysis, the annual risks of tuberculous infection in 1979 in the Netherlands were estimated to be 6, 9, 12, and 16 in 100 000 boys aged 5,10,15 and 20 years respectively, and 6,9,11 and 15 in 100 000 girls.

Dans une Etude anterieure, des estimations ont 6th faites des risques annuels d’infection tuberculeuse aux Pays-Bas de 1910 B 1966, a partir d’enquetes tuberculiniques chez des recrues et des Bcoliers. Le risque a decru de faGon particulitire- ment rapide ap& I’annGe 1940 environ (la diminution annuelle du risque Btait d’environ 13 %), et I’on a effect& sur cette base des projections concernant le risque jusqu’aux an&es 1980.

*This is a report of the Tuberculosis Surveillance Research Unit (TSRU) established by the International Union Against Tuberculosis (IUAT) in collaboration with the World Health Organisation (WHO). tDr J. Meijer died on 1 March 1983.

242 Sutherland and others

Les resultats des tests tuberculiniques chez des recrues masculines et parmi les enfants des Bcoles primaires et secondaires entre 1966 et 1979 ont maintenant Bte utilises, seuls ou avec du materiel anterieur, pour estimer ce qu’a 6th la tendance Obvolutive du risque d’infection tuberculeuse aux Pays- Bas jusqu’en 1979 et pour Studier les profils du risque en fonction de I’Bge et du sexe.

Le risque d’infection a continue a diminuer de facon rapide au tours des an&es, aux Pays-Bas. Parmi les recrues, le risque, estime a partir des don&es de 1969 a 1979, a decru de IO,4 % par an contre 13,7 % par an d’apres les estimations faites a partir des donnees plus anciennes concernant 1956 a 1966; cette difference n’est pas significative.

L’analyse des donnees completes concernant les ecoliers de 1956 a 1979 montre une diminution de leur risque d’infection de 15,0% chaque an&e. Les risques d’infection ont 6th les memes chez les garcons et chez les filles jusqu’a I’age de 10 ans, mais ils Btaient plus dleves de IO,2 % chez les garcons par rapport aux filles au tours de I’adolescence. De plus il y a eu une augmentation du risque de I’ordre de 6,l % par an pour chaque annee d’8ge jusqu’a I’Bge de 20 ans. D’apres cette analyse, on a estime que les risques annuels d’infection tuberculeuse en 1979 aux Pays-Bas on 6th de 6, 9, 12 et 16 cas d’infection par 100 000 garcons zig& respectivement de 5, 10, 15 et 20 ans et de 6, 9, 11 et 15 infections par 100 000 filles.

Resumen En un estudio previo se hicieron estimaciones del riesgo anual de infeccidn tuberculosa en Holanda entre 1910 y 1966, a partir de encuestas tuberculinicas realizadas en escolares y reclutas de las fuerzas armadas. El riesgo disminuyd de manera especialmente brusca despues de 1940 aproximadamente (la disminucion anual del riesgo foe de alrededor de 13 %) y sobre esta base, se hicieron proyecciones del riesgo hasta 10s afios 1980.

Los resultados de las pruebas tuberculinicas hechas en reclutas masculines y en estudiantes primarios o secundarios entre 1966 y 1979 han sido utilizados ahora, solos o combinados con el material anterior, para estimar la tendencia del riesgo de infeccidn tuberculosa en Holanda hasta el aAo 1979 y para estudiar 10s perfiles de este riesgo en funcidn del sexo y de la edad.

El riesgo de infection continua disminuyendo rapidamente a traves de 10s afios- calendario en Holanda. Entre 10s reclutas el riesgo estimado tinicamente a partir de 10s datos de 1966 a 1979, acusa una disminucion de 10.4 % anual, comparada con 13.7 % estimado a partir de datos anteriores: de 1956 a 1966; esta diferencia no es significativa.

El analisis de la totalidad de 10s datos referentes a 10s escolares desde 1956 a 1979 muestra una disminucidn del riesgo de infection de 15 % cada atio calendario. El riesgo de infeccidn fue similar en 10s nifios de 10s dos sexos hasta la edad de 10 aAos pero, durante el period0 de la adolescencia fue 10.2 % m& alto para 10s nifios de sexo masculine. Ademas habfa un aumento del riesgo de 6.1 % por cada afio de edad hasta la edad de 20 afios. Segun estos analisis, el riesgo anual de infection tuberculosa en 1979 en Holanda fue estimado en 6, 9, 12 y 16 cases de infecci6n por 100 000 niiios de 5,10,15 y 20 adios de edad y de 6,9,11 y 15 por 100.000 niAas, respectivamente.

The risk of tuberculous infection 243

Introduction Estimates of the annual risk of tuberculous infection in the Netherlands for the period from 1910 to 1966 were presented in the first report of the TSRU [I 1. It was shown that the trend in the annual risk of infection, derived from prevalence data, was uniformly downward. The risk of infection decreased steadily from an estimated risk of 9.7 % in 1913 to 2.4 % in 1939 (the annual decrease in log risk during this period being about 5 %), and to an estimated risk of only 0.058 % in 1966 (the annual decrease in log risk after 1939 being 13 %.) It is of particu- lar interest that over each of these two periods of about 25 years, the trend in the risk of infection in the Netherlands apparently closely followed an exponential decline. Because the decrease in the risk of infection had been so regular since 1940, a projection was made, assuming that the same trend would continue after 1966. According to this projection, the estimated risk of infection in 1979 would be 0.010 %, or 1 infection per 100 000 population.

The aim of the present paper is first to compare the average (all ages) risks of infection between 1967 and 1979, as predicted from the data available up to 1966 [I ] with those derived from the subsequent prevalence data only; and then to estimate the risks of infection in the Netherlands by calendar year and by age for the same period, using all the available data.

Methods The risks of infection by calendar year and by age were estimated by the methods described by Sutherland and Fayers [2] which represent an improvement and an extension of the methods previously used [l 1.

In the earlier report the critical diameter of induration, to distinguish subjects infected with virulent tubercle bacilli from uninfected subjects, was taken to be 8 mm. Thus, those with O-7 mm induration to 1 TU of tuberculin (with Tween 80), following the standard WHO tuberculin test, were regarded as having escaped tuberculous infection, and those with 8 mm induration or more were regarded as having been infected with tubercle bacilli at some time in the past.

The tuberculin surveys in recruits and in schoolchildren in the Netherlands were made by separate teams. In recruits the tuberculin test results were tabulated from 1956 to 1979 according to single millimetres of induration, so that it is readily possible to use a critical diameter other than 8 mm, if desired. However, in school children the results were presented only according to an 8 mm and a 10 mm criterion until 1965, and according to a 6 mm and a 10 mm criterion from 1966 onwards. Thus the only criterion which is consistently available for all tested groups throughout the whole period from 1956 onwards is IO mm, and this criterion has therefore been used in most of the analyses in the present paper.

Material Use of information from army recruits tested from 1956 to 1979

The results of the annual tuberculin surveys of male recruits carried out between 1956 and 1966 were used as the basis for estimating the calendar trend in the annual risk of tuberculous infection in the Netherlands during the first 20 years of the post-war period [I 1. The same tuberculin testing and reading techniques were used in the surveys during the period 1967 to 1979. As before, the surveys covered about 50 percent of the male population. The results for the whole period 1956 to 1979, according to the 8 and 10 mm criteria, are shown in Appendix Table A.

At this point two comments are necessary :

a It has been discovered only recently that the average age of the recruits at the time of


tuberculin testing was not 19.5 years, as reported by Styblo et al. [I ] but more than 20 years throughout the whole period from 1956. This had a slight effect on the /eve/ of the risks of infection derived in the earlier report, but not on the estimate of the calendar trend in the risk. For the present report an average age of 20.9 years has been used for all the data on recruits, this being the average age of a group of 300 recruits tested during March - May 1976. The great majority of these were aged 19,20 or 21 years.

b The information from the surveys in 1969 to 1972 inclusive has not been used because the findings were affected by the inclusion of recruits who had oral BCG vaccination at birth in 1950 or 1951 [3].

Use of the information from schoolchildren aged 72 to 18 years tested from 1966 to 1970

The results of the annual tuberculin surveys in schoolboys and schoolgirls aged about 12 to 18 years from 1962 to 1966 were used, in conjunction with the data from recruits, for the estimation of the risk of infection according to calendar year by Styblo et al. [I 1. The tuberculin testing and reading techniques were the same as for the army recruits, although different testing teams were used; the techniques have remained unchanged since. The tuberculin surveys were discontinued in schoolchildren of this age-group in autumn 1970. The data for 1966 to 1970, according to the 10 mm criterion, are shown in Appendix Table B.

Two comments have to be made about these data :

1. The schoolchildren were listed according to the age attained during the calendar year of testing, irrespective of whether they were tested before or after their birthday anniversary. The average age of the children listed as (say) 12 years is therefore 12.0, not 12.5 as taken previously [I 1. As with the recruits this had a slight effect on the level of the estimated risks of infection in that report.

2. Because of the influence of oral BCG vaccination at birth in 1950 and 1951 [3] the tuberculin test results for these two cohorts of children have been excluded from the present analysis, as follows : 1962-age 12; 1963-ages 12 and 13; 1964-ages 13 and 14; 1965- ages 14 and 15 ; 1966-ages 15 and 16 ; 1967-ages 16 and 17 ; 1968-ages 17 and 18; 1969-age 18.

Use of the information from schoolchildren aged 6 to 14 years tested from 1970 to 1973

The tuberculin surveys in schoolchildren aged 12 to 18 years were discontinued during 1970 and testing of schoolchildren in primary schools was introduced instead. The data for 1970 to 1973, according to the 10 mm criterion, are shown in Appendix Table C. None of these data were affected by oral BCG vaccination at birth.

The tuberculin testing of all schoolchildren throughout the Netherlands was discontinued in 1973. Instead, in 1974 and subsequent years, a sample of about 30 000 schoolchildren aged 9 to 12 years was selected for survey from three provinces only, for surveillance of the risk of infection among schoolchildren in regions where a relatively high risk was expected. About one-third of the children from the selected provinces were tested annually, so that a ‘round’ was completed in three years. The data for 1974 to 1977 are now available. They cannot be regarded as representative and have not been included in the calculation of the risk of infection ; but they are referred to again below.

Results The calendar trend in the risk of tuberculous infection

The calendar trend in the risk of tuberculous infection since 1940 was estimated by Styblo


et al. [I ] from the surveys in recruits in the 11 years 1956 to 1966. The surveys in recruits have now continued for a further 13 years.

Table I shows the estimates of the risk of infection from 1967 to 1979, as calculated from the data for 1956 to 1966, using the 8 mm criterion for tuberculous infection. A few small corrections have been made to these data, and this explains why the estimated annual decrease in log risk, 13.70 %, differs from the earlier figure of 13.79 % [I 1. The estimated annual risks of infection decrease from 0.044 % in 1967 to 0.009% in 1979. These are slightly lower than the earlier projections (which decreased from 0.051 to 0.010 %, because the average age of the recruits has now been taken as 20.9 instead of 19.5 years.

Table I also presents corresponding estimates calculated from the new data on recruits from 1967 to 1979 (excluding 1969 to 1972, as explained above). The estimated decrease in log risk is 10.41 % each year. The estimated risks of infection from the new data are rather higher than those based on the earlier data, decreasing from 0.079 % in 1967 to 0.023 % in 1979 (Fig. 1).

If the trend in log risk of infection is estimated from the data for the entire period to 1979 (apart from 1969 to 1972), the estimate is a decrease of 11.82 % annually, which is slightly lower than the estimate of 13.70 % from the data for 1956 to 1966 alone. However, the difference between these downward slopes is not great, and it is not yet possible to decide

Table I. Estimates of risk of tuberculous infection in the Netherlands from 1967 to 1979, predicted from the data on male recruits from 1956 to 1966, estimated from the observed data for 1967 to 1979, and estimated from the complete data from 1956 to 1979 (taking induration of 8 mm or more in the tuberculin test to indicate tuberculous infection)

Year Annual risk of infection (percent)

Predicted from data for 1956-66

Estimated from data for 1967-79*

Estimated from complete data 1956-79*

1967

1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979

0.044 0.079 0.039 0.071 0.034 0.064 0.029 0.058 0.026 0.052 0.022 0.047 0.019 0.042 0.017 0.038 0.015 0.034 0.013 0.031 0.011 0.028 0.010 0.025 0.009 0.023

0.067 0.060 0.053 0.047 0.042 0.037

0.029 0.026 0.023 0.021 0.018 0.016

Annual decrease -13.70 in log risk (%)

- 10.41 -11.82

*Excluding 1969-72; see text. Calculated from In(risk) = In(- In(1 - risk)) = c + s (year) entering the years as 67.5, etc. For 1956-66 data : c = + 1.5262; s = -0.1370. For 1967-79* data : c = -0.1136; s = -0.1041. For 1956-79* data : c = $0.6726; s = -0.1182.


%

10

5

1

0.5

0.1

0.05

0.01

0.005

0.001

\

\

\

from tests In recruits 1967-1979

\7 per 100,000

I I I I I I I I ._-_

100

50

10

5

1 1910 1930 1950 1970 1990

Figure 1. Annual risk of tuberculous infection, The Netherlands, 191 O-2000.

whether the rate of decrease of the risk of infection is really less steep than was estimated previously. Further observations are necessary to establish or exclude the reality of this lesser decrease.

If the 10 mm criterion for tuberculous infection is used instead of the 8 mm criterion, the downward trend, estimated from the entire data, is 12.04 % annually.

Estimated risks of infection by calendar year and age

The data among schoolchildren aged 12 or more from 1962 to 1966 were analysed together with those on recruits by Sutherland and Fayers [2], using 8 mm induration as the criterion of infection. The analysis showed a downward calendar trend in log risk of 14.7 %, and an upward trend with each year of age, of 4.2 %. The data now available on schoolchildren are much more extensive, consisting of information at ages 12 to 18 from 1962 until 1970


(omitting the data from two cohorts affected by oral vaccination at birth), supplemented with information at ages 6 to 14 from 1970 to 1973 (using 10 mm induration or more throughout as the criterion of infection). For a reason explained below, these extended data on schoolchildren were analysed separately from those for recruits. The data were prepared separately for males and females, and the percentages were pooled for the analysis. Differences in the risk of infection between the sexes will be examined below.

The annual trends in log risk, estimated from the extended data on schoolchildren, were a downward trend of 15.04 % for each calendar year, and an upward trend of 6.06 % for each year of age, these being in fairly close agreement with the findings from the data up to 1966 for the older schoolchildren. The corresponding estimates of the risks of infection each year from 1967 to 1979, at ages 5, 10, 15 and 20, are shown in Table II.

The observed prevalences of tuberculous infection in the various surveys (both sexes) are compared in Table III with the prevalences expected according to the estimated risks of infection by age and calendar year. The agreement is generally good. The observed prevalence in the cohorts born in 1950 and 1951, which are affected by oral vaccination at birth, exceed the expected values at ages 14 or more, the differences being particularly large for the 1951 cohort [3]. After 1970 the observed prevalences are consistently greater than those expected at ages 6-9 years, but at ages 1 O-l 2 years there is close agreement.

Reference was made above to the selective tuberculin testing of children aged 9 to 12 years from 1974 onwards in three provinces only. Table IV shows the results of these tests from 1974 to 1977, together with the prevalences expected from the experience for the whole of the Netherlands, as summarised in Table Ill. At each age in each year the prevalences were about double those expected from the national experience. This contrasts with the good agreement in this age range in the previous few years (see Table Ill) confirming that the selective testing, as intended, had been concentrated in areas with above-average risks of infection.

In view of the finding of a downward annual trend in log risk among the recruits of 12.04 % with calendar year, the above calculations were repeated, fixing the downward trend with

Table II. Estimated risks of tuberculous infection in the Netherlands by calendar year and age- 1967 to 1979: Ages 5, 10, 15 and 20 years (taking induration of 10 mm or more in the tuberculin test to indicate tuberculous infection)

Year Risk of infection (percent) at exact age

5 10 15 20

1967 0.039 0.053 0.071 0.097 1968 0.034 0.045 0.061 0.083 1969 0.029 0.039 0.053 0.072 1970 0.025 0.034 0.045 0.062 1971 0.021 0.029 0.039 0.053 1972 0.018 0.025 0.034 0.046 1973 0.016 0.021 0.029 0.039 1974 0.014 0.018 0.025 0.034 1975 0.012 0.016 0.021 0.029 1976 0.010 0.014 0.018 0.025 1977 0.009 0.012 0.016 0.021 1978 0.007 0.010 0.014 0.018 1979 0.006 0.009 0.012 0.016

Calculated from: In(risk) = In(-ln(l-risk) = c + r(age) + s(year) entering the years as 67.5, etc. with : c = 1.9976; r = $0.0606; s = -0.1504.


Table Ill. Observed and expected prevalence of tuberculous infection in the Netherlands 1962-l 973

Exact Prevalence Prevalence of tuberculous infection (percent)

wa (percent) 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973

6

7

8

9

10

11

12

13

14

15

16

17

18

Observed Expected Observed Expected Observed Expected Observed Expected Observed Expected 0 bserved Expected 0 bserved Expected Observed Expected 0 bserved Expected Observed Expected Observed Expected Observed Expected Observed Expected

0.35 0.31 0.23 0.21 0.18 0.16 0.31 0.32 0.43 0.27 0.23 0.20 0.36 0.39 0.71 0.35 0.30 0.26 0.89 0.49 0.33 0.47 0.44 0.38 0.32 0.28 0.67 0.42 0.39 0.47 0.54 0.47 0.40 0.35 0.66 0.54 0.52 0.53 0.67 0.57 0.49 0.43

2.92 2.46 1.89 1.50 1.20 1.24 1.08 0.92 0.72 0.68 0.68 0.69 2.70 2.32 2.00 1.72 1.48 1.28 1.10 0.95 0.82 0.70 0.60 0.52 3.34 2.72 2.60 2.36 1.43 1.43 1.26 1.11 0.88 1.03 1.45 1.73 3.25 2.81 2.42 2.08 1.80 1.55 1.33 1.15 0.99 0.85 0.73 0.63 4.00 3.42 2.77 3.10 1.86 1.69 1.56 1.40 1.10 3.92 3.38 2.91 2.51 2.16 1.87 1.61 1.38 1.19 4.79 4.04 3.36 3.15 3.13 2.14 1.87 1.77 1.27 4.69 4.05 3.49 3.01 2.59 2.24 1.93 1.66 1.43 5.56 4.86 4.09 3.92 3.17 3.41 2.35 2.11 1.74 5.59 4.83 4.17 3.59 3.10 2.67 2.30 1.99 1.71 6.13 5.46 4.89 4.58 3.72 3.42 3.80 2.54 1.99 6.63 5.73 4.95 4.28 3.69 3.18 2.75 2.37 2.04 7.53 6.40 5.64 5.27 4.28 3.90 3.74 4.11 2.60 7.84 6.78 5.86 5.07 4.37 3.78 3.26 2.81 2.42

Calculated from: In(1 - prevalence) = {exp(c + s(year - age))).{1 - exp((r -k s).age)}/(r + s). with: c = +1.9976; r = 0.0606; s = -0.1504. The observed values which are underlined relate to the two cohorts affected by oral vaccination at birth, and have not been used in computing the trends.

calendar year at 12.04% instead of the unconstrained value of 15.04 %. However, the data on schoolchildren did not fit this model nearly so well, indicating that the downward trend among the schoolchildren was apparently different from, and steeper than, that among recruits. (This is the main reason why the two sets of data were not amalgamated; the ex- planations for the different trend among the recruits, and for the possibility that this trend may have become slightly less steep in recent years, are not clear).

Estimated risks of infection by sex The data for male and female schoolchildren were reanalysed separately, fixing the trend in log risk with calendar year at -15.04 % and the trend with year of age at t6.06 %.

For the schoolchildren aged 12-l 8 years (tested from 1962 to 1970) the estimated values of c (see the formula at the foot of Table II) were 2.0324 for males and 1.9303 for females. The difference between them, 0.1021 or 10.2 %, represents the percentage excess of the risk of infection among males above that for females, during adolescence. The data available up to 1966 were examined similarly by Styblo et a/. [I ] ; from these data the excess among males was estimated to be about 9 percent.


Table IV. Observed prevalence of tuberculous infection in three selected provinces in the Netherlands, and the expected prevalence from the national experience. Ages 9-12 years, 1974 to 1977 (taking induration of 10 mm or more in the tuberculin test to indicate tuberculous infection)

Exact Prevalence

age (percent) Prevalence of tuberculous infection (percent)

1974 1975 1976 1977

9 Observed 0.61 0.50 0.43 0.31 Expected 0.24 0.21 0.18 0.15




The expected values are calculated from the same formula, using the same values of c, r, and s, as those for the Netherlands as a whole in Table 3.

An examination of the prevalence of tuberculous infection among the younger children shows little or no difference between the sexes at ages 6-12, indicating that the risk of infection is similar for pre-adolescent boys and girls. The estimated risks shown at ages 5 and 10 in Table II therefore apply to either sex. Table V shows the estimated risks of infection in males and females separately at ages 15 and 20 for the period 1967 to 1979 (the risks in Table II being estimates for the sexes combined).

Table V. Estimated risks of tuberculous infection in the Netherlands by calendar year, age and sex-l 967 to 1979 : ages 15 and 20 years

Year Risk of infection (percent) at exact age

Male

15 20

Female Male Female

1967 0.074 0.067 0.100 0.090 1968 0.064 0.057 0.086 0.078 1969 0.055 0.049 0.074 0.067 1970 0.047 0.042 0.064 0.058 1971 0.040 0.037 0.055 0.049 1972 0.035 0.031 0.047 0.043 1973 0.030 0.027 0.041 0.037 1974 0.026 0.023 0.035 0.032 1975 0.022 0.020 0.030 0.027 1976 0.019 0.017 0.026 0.023 1977 0.016 0.015 0.022 0.020 1978 0.014 0.013 0.019 0.017 1979 0.012 0.011 0.016 0.015

Calculated from the same formula as for Table II. For males : c = 2.0324;

1 I= +0.0606; s = -0.1504

For females : c = 1.9303;


Discussion The most direct and sensitive method for detecting whether there is a calendar trend in the risk of tuberculous infection in an area, and for assessing its magnitude, is to make several representative tuberculin surveys at intervals among unvaccinated subjects, testing subjects of the same age (or the same average age) on each occasion. The series of tuberculin surveys of male army recruits in the Netherlands, which started in 1956 and has now continued, with unchanged techniques, for more than 25 years, is almost certainly the best and most in- formative material of this type. About 40 000 recruits, with an average age of about 20.9 years, are included each year, and this represents about half of each annual male population cohort in the Netherlands.

The original study of the first 11 years of this material in the first TSRU report [I ] showed that there had been a steep downward calendar trend in the risk of tuberculous infection during the lifetime of the cohorts tested, approximating closely to an exponential decrease of more than 13 % each year. These data were used to estimate the annual risks of tuberculous infection until 1966, and, assuming a continuation of the same downward trend, projected estimates of the risk were made from 1967 to 1980.

At the time of that report, many people considered that the trend which had been estimated was much too steep, and that the risk could not possibly continue to decrease at that rate. The present study has therefore used the next 13 years of these data, from 1967 to 1979, in two ways. First, they have been analysed without reference to the earlier data, and so have provided an independent estimate of the calendar trend in the risk between 1967 and 1979. The downward calendar trend from the new data was 10.4 % annually compared with 13.7 % from the old data, a non-significant difference. Secondly, the old and new data have been combined to provide an updated estimate of the trend until 1979, and revised estimates of the risks from 1967 to 1979.

These comparisons show that, despite the misgivings at the time, the trend of the risk of infection, estimated from the data until 1966, was a good predictor of the trend from 1967 onwards. It is thus to be expected that the updated estimate of a downward trend of 11.8 % annually until 1979 will also represent a good predictor of the trend from 1980 onwards. It is planned to continue the tuberculin surveys in the Netherlands recruits throughout the 1980’s and these will provide further information on this point. The results of the surveys in 1980 and 1981 are included in Appendix Table A, and show further decreases in the prevalence of tuberculous infection in recruits after 1979.

There is a suggestion from these analyses that the trend in risk in the future may be slightly less steep than in the past, but this is not certain, and even if it occurs it will be of small practical importance. The revised estimate of the risk of infection for the recruits in 1979 was 0.016 %, or 16 per 100 000, and the estimated downward trend corresponds to a halving of this risk every 6 years (compared with every 5 years from the earlier data). Even if this extends to every 7 or 8 years, the levels of risk by 1990, and especially by the year 2000, will still be vanishingly low.

Findings of tuberculin surveys in schoolchildren in the Netherlands were also analysed in the earlier report and provided information on variations in the risk of tuberculous infection with sex and with age. The extended data analysed here show that superimposed on a downward calendar trend of 15 % per year there is an increase in log risk of infection from birth to age 20 of about 6 % per year of age; the reasons would seem to be both environmental and physiological. In younger children the risks of infection for boys and girls are the same, but during adolescence the risks for males rise about 10 % above those for females. A similar pattern with sex and age has been noted in many other countries and in very different cultures, and the reasons therefore seem to be physiological and not environmental.


The figures analysed here refer only to the resident Dutch population of the Netherlands. The country has since 1960 welcomed a large number of foreign workers with higher tuberculosis rates than the general Dutch population. In addition there are many visitors to the Netherlands each year from countries with larger tuberculosis problems, and many of the Dutch population visit such countries themselves. The steep decreases in the risk of infection are therefore occurring in spite of these outside opportunities for tuberculous infection. The findings in the Netherlands suggest that in other developed countries the risks of tuberculous infection are also capable of decreasing steeply to a point at which tuberculosis has been virtually eliminated.

References 1 Stqblo, K., Meijer, J., Er Sutherland, I. (1969). The transmission of tubercle bacilli. Its trend in a human population.

Tuberculosis Surveillance Research Unit Report No. 1, Bulletin of the international Union against Tuberculosis, 42, 5.

2 Sutherland, I., Et Fayers, P. M. (1975). The association of the risk of tuberculous infection with age. Bulletin of the International Union against Tuberculosis, 50, 70.

3 Bleiker, M. A., Meijer, J., St)sblo, K., Et Sutherland, I. (1983). The persistence of tuberculin sensitivity following oral BCG vaccination in the Netherlands. Tuber&e, 64, 255.

Appendix Table A. Results of tuberculin testing in unvaccinated male recruits (average age 20.9 years)-The Netherlands, 1956-l 979

Year of Number induration > 10 mm Induration 28 mm survey tested Percent Percent

-

1956 40217 19.1 a 21.52 1957 38 163 16.33 18.51 1958 37 365 15.20 17.21 1959 41 101 13.58 14.66 1960 42 870 11.90 12.91 1961 44918 10.95 11.80 1962 45124 9.09 9.90 1963 44 600 7.67 8.39 1964 38 395 6.90 7.49 1965 38 999 6.31 7.07 1966 42 468 5.45 6.07 1967 34177 4.97 5.54 1968 41 613 4.68 5.20 1969 41 035 4.37 4.86 1970 37 762 4.35 4.93 1971 44 092 4.47 4.99 1972 38 460 3.65 4.08 1973 41 628 2.72 3.26 1974 40 554 2.45 2.80 1975 38 473 2.27 2.64 1976 38 082 2.1 a 2.61 1977 42 987 2.07 2.43 1978 42 013 1.27 1.51 1979 44 665 1.17 1.41

1980 45 895 0.85 1.05 1981 45 893 0.84 1.04


Appendix Table B. Results of tuberculin testing in unvaccinated schoolchildren, aged 12 to 18 years-The Netherlands, 1966-l 970

Year of survey

&a (nearest birthday)

Males

Number tested

Induration > 10 mm Percent

Females

Number tested


1966 12 19818 1.20 20 898 1.21 13 55 573 1.55 59 357 1.31 14 76 069 1.93 72109 1.79 15 71 374 3.38 57 004 2.83 16 57 274 3.27 39 892 3.03 17 40 962 3.73 25 435 3.69 18 26 289 4.32 13961 4.20

1967 12 22 297 1.36 23 967 1.13 13 56 705 1.53 58154 1.33 14 74 578 1.82 70 005 1.54 15 72 524 2.29 57 683 1.96 16 55 423 3.67 37 092 3.01 17 39710 3.53 23 069 3.23 18 24 878 4.00 11 940 3.71

1968 12 23013 1.08 23 884 1.07 13 55 662 1.35 57816 1.18 14 72 714 1.63 68 243 1.49 15 69 647 1.98 56 704 1.75 16 56 824 2.41 38 992 2.25 17 38 309 3.99 22 460 3.48 18 24 268 3.87 11 592 3.46

1969 12 21 755 0.93 23 322 0.90 13 54 467 1.14 55 538 1.07 14 69 774 1.50 65 500 1.30 15 68 945 1.91 54 636 1.61 16 55 572 2.18 37 433 1.99 17 39 479 2.57 22 242 2.49 18 23 040 4.21 10282 3.89

1970 12 18241 0.61 18833 0.63 13 36 478 0.86 35312 0.75 14 42 351 1.10 37 757 1.04 15 38 757 1.29 29 762 1.24 16 30 665 1.81 18499 1.63 17 20 287 2.08 10184 1.83 18 12212 2.67 4504 2.42


Appendix Table C. Results of tuberculin testing in unvaccinated schoolchildren, aged 6 to 14 vears-The Netherlands, 1970-l 973

Year of survey

Age (nearest birthday)

Males

Number tested


Females

Number tested

induration > 10 mm Percent

1970 6 20 821 0.31 20 047 0.38 7 54 581 0.34 51 379 0.28 8 22114 0.35 18865 0.38 9 4151 0.67 3169 1.17

10 17136 0.65 17432 0.69 11 41 345 0.70 41 666 0.61 12 28 495 0.79 25 631 0.78 13 9895 1.09 7638 1.28 14 2946 1.90 1873 1.33

1971 6 9105 0.21 8769 0.42 7 49 765 0.33 46 561 0.31 8 21 944 0.41 18593 0.37 9 12161 0.53 12105 0.44

IO 22 886 0.44 23213 0.40 11 45519 0.55 44 968 0.53 12 27 326 0.69 23 843 0.66 13 7272 1 .oo 5198 1.08

1972 6 1076 0.28 1078 0.18 7 1500 0.33 1307 0.54 8 1040 0.67 794 0.76 9 9018 0.39 9247 0.28

10 37415 0.34 38 877 0.43 11 45 256 0.53 44 028 0.50 12 18951 0.68 16348 0.69 13 3691 1.30 2595 1.66

1973 9 1741 0.34 1898 0.58 10 15070 0.43 15891 0.52 11 20 946 0.51 20 407 0.54 12 9024 0.79 7925 0.58 13 1522 1.31 1026 2.34

the risk of tuberculous infection in the netherlands from 1967 to 1979

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